Abstract
Cholesterol is an essential component of the cell membrane. In the human body, approximately 1/3 of plasma cholesterol can be found in free form whereas that 2/3 is found in the form of esters, mainly with linoleic and oleic acids.
The main source of cholesterol in the human body comes from diet (~ 2/3), the remaining 1/3 of cholesterol is synthesized de novo from its basic component, i.e. active acetate. Quantitatively speaking, a substantial portion of the cholesterol needed for biological processes is obtained from the diet under normal circumstances.
However, cholesterol absorption is a very complex process that depends on the function of specific carriers in the brush border of enterocytes in the jejunum. Its absorption efficiency has been estimated in 50%-60%, depending on the cholesterol content in the diet.
During the day, an average of 250-500 mg of cholesterol is absorbed. This amount is regulated by the nuclear receptor of enterocytes, in which the ATP-binding cassette AP proteins (ABC), and the G5 and G8 cotransporters, play an important role in cholesterol absorption (Kramer et al., 2005).
These proteins are expressed on the bile pole of hepatocytes and allow the transport of sitosterol and cholesterol from these cells into the bile. Mutations in these proteins can result in sitosterolemia, a rare metabolic disorder associated with a marked increment of sitosterol in the body.
This disorder is characterized by the early development of atherosclerosis.Under physiological conditions, the synthesis de novo of cholesterol in all tissues of the organism can surpass the quantity absorbed from diet. Indeed, all cells in the human body, with the exception of erythrocytes, are able to synthesize cholesterol de novo; however, this cholesterol is mostly intended for intracellular metabolism.
Although plasma cholesterol, aimed toward the activation of the lipoprotein cascade, is synthesized in the liver and in small bowel. This fraction of cholesterol is intended for the needs of individual organs.
Unlike vertebrates, plants synthesize a wide group of phytosterols (sitosterol, campesterol, brasicasterol, etc.) instead of cholesterol. Phytosterols are different metabolically and functionally from cholesterol.
Only fungi that are metabolically similar to animal cells in many ways (for example, they synthesize glycogen) produce in insignificant amounts cholesterol instead of phytosterols. Cholesterol synthesis takes place in the cytoplasm until the intermediate product squalene emerges and its synthesis continues in the endoplasmic reticulum (squalene cyclization and other metabolic steps).
The key enzyme for cholesterol synthesis is HMG-CoA reductase, of which statins are a competitive pharmacological inhibitor. Given the complexity of cholesterol synthesis, it is not surprising that higher organisms use cholesterol from external sources, usually synthesized by lower organisms, thus saving the energy and metabolic burden that would otherwise be spent in the synthesis process.
It is for this reason that most tissues of the human body obtain cholesterol from plasma lipoproteins for cellular structures and functions rather than from intracellular synthesis. Moreover, it is clear that cholesterol synthesis, due to its metabolic complexity and energy-demanding nature, usually takes place during sleep in primates and humans, i.e. a period of reduced metabolic activity for the organism.
Cholesterol synthesis can be monitored through the production of isoprene, which is a fundamental building block of cholesterol and it is formed by endogenous synthesis. Isoprene is highly volatile and thus can be measured in the exhaled breath of a person.
In this manner, the diurnal intensity of cholesterol synthesis can be determined. The maximum rate of cholesterol synthesis in a healthy person can reach as much as 0.5-1 g in 24 h, mainly occurring between 2:00 and 3:00 a.m.